{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:03:29Z","timestamp":1788897809523,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014NextGenerationEU","award":["CUP [B53C22006080001]"],"award-info":[{"award-number":["CUP [B53C22006080001]"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease. Quantifying neuronal damage is a critical step for patient care. Neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are the most promising serum biomarkers reflecting neuronal damage and astroglial activation, respectively. This study analyzed sNfL and sGFAP in 177 MS patients and 71 healthy controls (HCs) using SIMOA technology, classifying patients as responders (Rs) or non-responders (NRs) based on \u201cNo Evidence of Disease Activity 3\u201d (NEDA-3) status during two years of treatment. Longitudinal analyses were performed for Dimethyl fumarate (DMF) and Ocrelizumab (OCRE) treatment. Biomarker\u2013age correlation analysis in HCs confirmed correlation between both NfL and GFAP, with age and cut-off values specific for age decades being calculated. Both biomarkers were higher in MS patients compared to HCs. sNfL showed a significant increase in NR patients overall. In contrast, sGFAP was elevated in the low-to-moderate-efficacy treatment agents (LETAs) NR group and also in the DMF NR subgroup, suggesting that it monitors persistent astrogliosis. Longitudinal analysis showed that both biomarkers decreased during DMF treatment after one year. During OCRE treatment, sNfL rapidly reduced to HC levels within one year, while sGFAP decreased only after two years. This highlights that OCRE acts differently on the pathological processes linked to the two biomarkers.<\/jats:p>","DOI":"10.3390\/ijms27031441","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:00:33Z","timestamp":1770022833000},"page":"1441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Differential Biomarkers of Response to Dimethyl Fumarate and Ocrelizumab in Multiple Sclerosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8008-0191","authenticated-orcid":false,"given":"Alessandra","family":"Mingione","sequence":"first","affiliation":[{"name":"Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, 20142 Milan, Italy"},{"name":"Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Corona","sequence":"additional","affiliation":[{"name":"Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, 20142 Milan, Italy"},{"name":"Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Monzani","sequence":"additional","affiliation":[{"name":"Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, 20142 Milan, Italy"},{"name":"Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0908-7469","authenticated-orcid":false,"given":"Alen","family":"Zollo","sequence":"additional","affiliation":[{"name":"Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, 20142 Milan, Italy"},{"name":"Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Cirocco","sequence":"additional","affiliation":[{"name":"Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2371-9591","authenticated-orcid":false,"given":"Tiziana","family":"Zaccone","sequence":"additional","affiliation":[{"name":"Clinical Neurology Unit, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8421-0210","authenticated-orcid":false,"given":"Mariangela","family":"Scavone","sequence":"additional","affiliation":[{"name":"Laboratory of Haemostasis and Thrombosis, Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Marco","family":"Podda","sequence":"additional","affiliation":[{"name":"Laboratory of Haemostasis and Thrombosis, Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Division of Medicina Generale SP, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2368-2393","authenticated-orcid":false,"given":"Paola","family":"Signorelli","sequence":"additional","affiliation":[{"name":"Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Biochemistry Laboratory, IRCCS Policlinico San Donato, 20097 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Miozzo","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Medical Genetics Unit, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1549-3851","authenticated-orcid":false,"given":"Alberto","family":"Priori","sequence":"additional","affiliation":[{"name":"Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Clinical Neurology Unit, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-1368","authenticated-orcid":false,"given":"Filippo","family":"Martinelli-Boneschi","sequence":"additional","affiliation":[{"name":"Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, 20142 Milan, Italy"},{"name":"Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Clinical Neurology Unit, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","article-title":"Neurofilaments as biomarkers in neurological disorders","volume":"14","author":"Khalil","year":"2018","journal-title":"Nat. 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